EGFR dysregulation has been linked to numerous cancers and both, small molecules and EGFR targeting antibodies have successfully reached the clinic. However, the antibodies approved for clinical use, and those in development, all share a severe side effect profile due to the broad normal tissue-expression of EGFR. The deletion variant III of EGFR (EGFRvIII), with truncated extracellular domain and ensuing ligand-independent constitutive activity, is the most common mutant form associated with oncogenic transformation. EGFRvIII is expressed exclusively in cancer tissues and is associated with various solid tumor types.